1. Sinapic Acid Mitigates Pentylenetetrazol-induced Acute Seizures By Modulating the NLRP3 Inflammasome and Regulating Calcium/calcineurin Signaling: In Vivo and In Silico Approaches.
- Author
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Ali SO, Ghaiad HR, Elmasry GF, and Mehana NA
- Subjects
- Animals, Mice, Male, Molecular Docking Simulation, Signal Transduction drug effects, Calcium Signaling drug effects, Oxidative Stress drug effects, Computer Simulation, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Calcium metabolism, Anticonvulsants pharmacology, Anticonvulsants therapeutic use, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Pentylenetetrazole, Calcineurin metabolism, Seizures chemically induced, Seizures drug therapy, Seizures metabolism, Inflammasomes metabolism, Coumaric Acids pharmacology, Coumaric Acids therapeutic use
- Abstract
Sinapic acid (SA) is a naturally occurring carboxylic acid found in citrus fruits and cereals. Recent studies have shown that SA has potential anti-seizure properties due to its anti-inflammatory, antioxidant, and anti-apoptotic effects. The present study investigated the neuroprotective role of SA at two different dosages in a pentylenetetrazol (PTZ)-induced acute seizure model. Mice were divided into six groups: normal control, PTZ, SA (20 mg/kg), SA (20 mg/kg) + PTZ, SA (40 mg/kg), and SA (40 mg/kg) + PTZ. SA was orally administered for 21 days, followed by a convulsive dose of intraperitoneal PTZ (50 mg/kg). Seizures were estimated via the Racine scale, and animals were behaviorally tested using the Y-maze. Brain tissues were used to assess the levels of GABA, glutamate, oxidative stress markers, calcium, calcineurin, (Nod)-like receptor protein-3 (NLRP3), interleukin (IL)-1β, apoptosis-associated speck-like protein (ASC), Bcl-2-associated death protein (Bad) and Bcl-2. Molecular docking of SA using a multistep in silico protocol was also performed. The results showed that SA alleviated oxidative stress, restored the GABA/glutamate balance and calcium/calcineurin signaling, downregulated NLRP3 and apoptosis, and improved recognition and ambulatory activity in PTZ-treated mice. In silico results also revealed that SA strongly interacts with the target proteins NLRP3 and ASC. Overall, the results suggest that SA is a promising antiseizure agent and that both doses of SA are comparable, with 40 mg/kg SA being superior in normalizing glutathione, calcium and IL-1β, in addition to calcineurin, NLRP3, ASC and Bad., Competing Interests: Declarations. Ethics Approval: All procedures involving the handling of the experimental animals were conducted in compliance with the NIH Guide for the Care and Use of Laboratory Animals. The Research Ethics Committee of the Faculty of Pharmacy, Cairo University (REC-FOPCU), approved this study under approval number BC 3199. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2024
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